人口Pharmacokinetic-Pharmacodynamic模型在健康志愿者口服氟氢可的松和静脉注射氢化可的松。
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Hamitouche N,彗星E, Ribot M,阿尔瓦雷斯JC, Bellissant E, Laviolle B
人口Pharmacokinetic-Pharmacodynamic模型在健康志愿者口服氟氢可的松和静脉注射氢化可的松。
aap j . 2017年5月,19 (3):727 - 735。doi: 10.1208 / s12248 - 016 - 0041 - 9。Epub 2017年1月12日。
- PubMed ID
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28083797 (在PubMed]
- 文摘
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本研究旨在描述药物动力学和氟氢可的松和氢化可的松的浓度效应关系在健康志愿者尿钠/钾排泄。这是一个安慰剂对照、随机、双盲、交叉研究中,口服氟氢可的松和静脉注射氢化可的松,鉴于单独或结合在一起,在12名健康男性志愿者。非线性mixed-effects建模是用来描述药物动力学和pharmacokinetic-pharmacodynamic关系上尿钠/钾比例为每一个药物。单舱模型被用来描述氟氢可的松和氢化可的松药物动力学。是指血浆半衰期为1.40 h (95% ci[0.80, 2.10])氟氢可的松为2.10 h (95% ci[1.78, 2.40])氢化可的松。间隙是40.8 L / h (95% ci[33.6; 48])对氟氢可的松和30 L / h (95% ci[25.3, 34.7])氢化可的松。一种间接响应模型是用来描述对尿钠/钾比的影响。氟氢可的松等离子体浓度显示更广泛的比氢化可的松inter-individual色散等离子体浓度。尿钠/钾比例变化与氟氢可的松和氢化可的松也更高。生产药物的血浆浓度50%的最大抑制尿钠/钾(IC50)低200倍氟氢可的松(0.08杯/ L, 95% ci[0.035, 0.125])比氢化可的松(16.7杯/ L, 95% ci [10.5, 22.9])。beplayapp Simulations showed that a 4-time per day administration regimen allow to achieve steady fludrocortisone plasma concentrations with stable decrease in urinary sodium/potassium ratio after the second administration of fludrocortisone. Fludrocortisone and hydrocortisone have short and similar plasma elimination half-lives in healthy subjects. Fludrocortisone plasma concentrations and effect on urinary sodium/potassium ratio had a higher inter-individual variability as compared to hydrocortisone. The administration regimen of fludrocortisone should be reconsidered.
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